Husain K
Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, Puerto Rico 00732, USA.
Cell Mol Biol (Noisy-le-grand). 2007 Apr 15;53(1):70-7.
Epidemiological studies in humans and experimental studies in animals have shown the link between chronic alcohol consumption and the prevalence of hypertension. However, molecular mechanisms implicated with alcohol-induced increases in blood pressure (BP) remain elusive. The objective of this study was to investigate the relationship between BP and molecular as well as physiological changes in aortic endothelium in chronic ethanol treated rats. Male Fisher rats were given 20% ethanol (4 g/kg) orally and controls received 5% sucrose daily for 12 weeks. The BP was recorded weekly by tail-cuff method and after 12 weeks, rats were anesthetized with pentobarbital, thoracic aorta isolated and used for aortic reactivity using tissue bath and for biochemical analysis. The data show that ethanol ingestion significantly increased systolic, diastolic and mean BP after 12 weeks compared to control. The endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expressions were down-regulated leading to depletion of aortic NO levels in ethanol treated rats compared to control. The aortic NADPH oxidase activity significantly enhanced with a concomitant increase in membrane lipid peroxidation and depressed ratio of reduced to oxidized glutathione in alcohol-treated rats compared to control. The aortic vasoconstriction was slightly enhanced in response to phenylephrine but vasorelaxation was significantly diminished in response to acetylcholine, adenosine and sodium nitroprusside in chronic ethanol treated rats. It is concluded that chronic ethanol ingestion induces aortic endothelial oxidative injury and the down regulation of nitric oxide generating system leading to impaired vasorelaxation and hypertension in rats.
人类流行病学研究和动物实验研究表明，长期饮酒与高血压患病率之间存在关联。然而，酒精导致血压（BP）升高所涉及的分子机制仍不清楚。本研究的目的是探讨慢性乙醇处理大鼠的血压与主动脉内皮分子及生理变化之间的关系。给雄性Fisher大鼠口服20%乙醇（4 g/kg），对照组每天给予5%蔗糖，持续12周。每周用尾套法记录血压，12周后，用戊巴比妥麻醉大鼠，分离胸主动脉，用于组织浴主动脉反应性测定及生化分析。数据显示，与对照组相比，摄入乙醇12周后收缩压、舒张压和平均血压显著升高。与对照组相比，乙醇处理大鼠的内皮型一氧化氮合酶（eNOS）和血管内皮生长因子（VEGF）表达下调，导致主动脉NO水平降低。与对照组相比，酒精处理大鼠的主动脉NADPH氧化酶活性显著增强，同时膜脂质过氧化增加，还原型谷胱甘肽与氧化型谷胱甘肽的比例降低。慢性乙醇处理大鼠对去氧肾上腺素的主动脉收缩反应略有增强，但对乙酰胆碱、腺苷和硝普钠的血管舒张反应显著减弱。结论是，长期摄入乙醇可诱导大鼠主动脉内皮氧化损伤和一氧化氮生成系统下调，导致血管舒张功能受损和高血压。
